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https://www.readbyqxmd.com/read/29777105/phenotypic-diversification-by-enhanced-genome-restructuring-after-induction-of-multiple-dna-double-strand-breaks
#1
Nobuhiko Muramoto, Arisa Oda, Hidenori Tanaka, Takahiro Nakamura, Kazuto Kugou, Kazuki Suda, Aki Kobayashi, Shiori Yoneda, Akinori Ikeuchi, Hiroki Sugimoto, Satoshi Kondo, Chikara Ohto, Takehiko Shibata, Norihiro Mitsukawa, Kunihiro Ohta
DNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29735400/concept-of-dna-lesion-longevity-and-chromosomal-translocations
#2
REVIEW
Nicholas R Pannunzio, Michael R Lieber
A subset of chromosomal translocations related to B cell malignancy in human patients arises due to DNA breaks occurring within defined 20-600 base pair (bp) zones. Several factors influence the breakage rate at these sites including transcription, DNA sequence, and topological tension. These factors favor non-B DNA structures that permit formation of transient single-stranded DNA (ssDNA), making the DNA more vulnerable to agents such as the enzyme activation-induced cytidine deaminase (AID) and reactive oxygen species (ROS)...
May 4, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29725125/development-of-a-generic-%C3%AE-lactamase-screening-system-for-improved-signal-peptides-for-periplasmic-targeting-of-recombinant-proteins-in-escherichia-coli
#3
Tania Selas Castiñeiras, Steven G Williams, Antony Hitchcock, Jeffrey A Cole, Daniel C Smith, Tim W Overton
Targeting of recombinant proteins to the Escherichia coli periplasm is a desirable industrial processing tool to allow formation of disulphide bonds, aid folding and simplify recovery. Proteins are targeted across the inner membrane to the periplasm by an N-terminal signal peptide. The sequence of the signal peptide determines its functionality, but there is no method to predict signal peptide function for specific recombinant proteins, so multiple signal peptides must be screened for their ability to translocate each recombinant protein, limiting throughput...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29714651/hypereosinophilic-syndrome-preceding-a-diagnosis-of-b-cell-lymphoma
#4
Arash Samarghandi, Shradha Ahuja, Vishal Jindal, Sorab Gupta, Ilmana Fulger
INTRODUCTION: Hypereosinophilic syndrome (HES) is a rare condition characterized by eosinophilia and organ destruction secondary to eosinophilic infiltration. The coexistence of primary B-cell lymphoma and hypereosinophilic syndrome is extremely rare. We present a case of HES that preceded the diagnosis of diffuse large B-cell lymphoma. CASE REPORT: A 70-year-old man presented with a 3-month history of diarrhea and 30-pound weight loss. Complete blood count showed a white blood cell count of 7452/µL with eosinophils of 42% (absolute eosinophil count 3130)...
March 1, 2018: Tumori
https://www.readbyqxmd.com/read/29713947/-1-h-15-n-and-13-c-resonance-assignments-of-the-j-domain-of-co-chaperone-sis1-from-saccharomyces-cerevisiae
#5
Glaucia M S Pinheiro, Gisele C Amorim, Anwar Iqbal, C H I Ramos, Fabio C L Almeida
Protein folding in the cell is usually aided by molecular chaperones, from which the Hsp70 (Hsp = heat shock protein) family has many important roles, such as aiding nascent folding and participating in translocation. Hsp70 has ATPase activity which is stimulated by binding to the J-domain present in co-chaperones from the Hsp40 family. Hsp40s have many functions, as for instance the binding to partially folded proteins to be delivered to Hsp70. However, the presence of the J-domain characterizes Hsp40s or, by this reason, as J-proteins...
April 30, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29689540/investigational-antiretroviral-drugs-what-is-coming-down-the-pipeline
#6
Roy M Gulick
Over the past 30 years, antiretroviral drug regimens for treating HIV infection have become more effective, safer, and more convenient. Despite 31 currently approved drugs, the pipeline of investigational HIV drugs remains full. Investigational antiretroviral drugs include the nucleoside analogue reverse transcriptase translocation inhibitor (NRTTI) MK-8591, a long-acting compound that could be dosed once weekly. Investigational nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) include doravirine, which is active in vitro against NNRTI-resistant HIV and was potent and well-tolerated when used in combination with a dual-nucleoside analogue RTI (nRTI) backbone in treatment-naive individuals...
April 2018: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/29686650/glucose-transporters-in-diabetic-kidney-disease-friends-or-foes
#7
REVIEW
Anita A Wasik, Sanna Lehtonen
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a common cause of end-stage renal disease worldwide. DKD manifests as an increased urinary protein excretion (albuminuria). Multiple studies have shown that insulin resistance correlates with the development of albuminuria in non-diabetic and diabetic patients. There is also accumulating evidence that glomerular epithelial cells or podocytes are insulin sensitive and that insulin signaling in podocytes is essential for maintaining normal kidney function...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29684214/new-perspectives-on-chloroplast-protein-import
#8
Masato Nakai
Virtually all chloroplasts in extant photosynthetic eukaryotes derive from a single endosymbiotic event that likely occurred more than a billion years ago between a host eukaryotic cell and a cyanobacterium-like ancestor. Many endosymbiont genes were subsequently transferred to the host nuclear genome, concomitant with the establishment of a system for protein transport through the chloroplast double-membrane envelope. Presently, 2000-3000 different nucleus-encoded chloroplast proteins must be imported into the chloroplast following their synthesis in the cytosol...
April 19, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29684146/genetic-structure-and-diversity-among-historic-and-modern-populations-of-the-sumatran-rhinoceros-dicerorhinus-sumatrensis
#9
Jessica R Brandt, Peter J Van Coeverden de Groot, Kelsey E Witt, Paige K Engelbrektsson, Kristofer M Helgen, Ripan S Malhi, Oliver A Ryder, Alfred L Roca
The Sumatran rhinoceros (Dicerorhinus sumatrensis), once widespread across Southeast Asia, now consists of as few as 30 individuals within Sumatra and Borneo. To aid in conservation planning, we sequenced 218 bp of control region mitochondrial (mt) DNA, identifying 17 distinct mitochondrial haplotypes across modern (N = 13) and museum (N = 26) samples. Museum specimens from Laos and Myanmar had divergent mtDNA, consistent with the placement of western mainland rhinos into the distinct subspecies D. s. lasiotis (presumed extinct)...
April 19, 2018: Journal of Heredity
https://www.readbyqxmd.com/read/29666625/dying-to-be-noticed-epigenetic-regulation-of-immunogenic-cell-death-for-cancer-immunotherapy
#10
REVIEW
Brianne Cruickshank, Michael Giacomantonio, Paola Marcato, Sherri McFarland, Jonathan Pol, Shashi Gujar
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various "hallmarks" of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29606793/quionolone-carboxylic-acid-derivatives-as-hiv-1-integrase-inhibitors-docking-based-hqsar-and-topomer-comfa-analyses
#11
Jianbo Tong, Pei Zhan, Xiang Simon Wang, Yingji Wu
Quionolone carboxylic acid derivatives as inhibitors of HIV-1 integrase were investigated as a potential class of drugs for the treatment of acquired immunodeficiency syndrome (AIDS). Hologram quantitative structure-activity relationships (HQSAR) and translocation comparative molecular field vector analysis (topomer CoMFA) were applied to a series of 48 quionolone carboxylic acid derivatives. The most effective HQSAR model was obtained using atoms and bonds as fragment distinctions: cross-validation q 2 = 0...
December 2017: Journal of Chemometrics
https://www.readbyqxmd.com/read/29595948/nanoporous-hydrogels-for-the-observation-of-anthrax-exotoxin-translocation-dynamics
#12
Christopher Baker, Ben Schudel, Mangesh I Chaudhari, Kerrie Wu, Derek Dunford, Anup K Singh, Susan B Rempe, Anson V Hatch
The ability to observe lethal anthrax exotoxins translocating through size-constricting nanopores in vitro, combined with detailed sequence and structural data, has aided in eluci- dated mechanisms of exotoxin cell entry and toxicity. However, due to limited observations of anthrax exotoxins translocating through protective antigen nanopores in vitro, and the instability of protective antigen-functionalized suspended lipid bilayers, questions remain re- garding the native mechanisms of cell entry. Nanoporous hydrogel membranes oer a robust tool for studying protein translocation with ensemble measurements that complement con- ventional single molecule translocation measurements...
March 29, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29587653/efficient-anchoring-of-alien-chromosome-segments-introgressed-into-bread-wheat-by-new-leymus-racemosus-genome-based-markers
#13
Offiong Ukpong Edet, June-Sik Kim, Masanori Okamoto, Kousuke Hanada, Tomoyuki Takeda, Masahiro Kishii, Yasir Serag Alnor Gorafi, Hisashi Tsujimoto
BACKGROUND: The tertiary gene pool of bread wheat, to which Leymus racemosus belongs, has remained underutilized due to the current limited genomic resources of the species that constitute it. Continuous enrichment of public databases with useful information regarding these species is, therefore, needed to provide insights on their genome structures and aid successful utilization of their genes to develop improved wheat cultivars for effective management of environmental stresses. RESULTS: We generated de novo DNA and mRNA sequence information of L...
March 27, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29545945/the-kinase-lrrk2-is-differently-expressed-in-chronic-rhinosinusitis-with-and-without-nasal-polyps
#14
Yue Ma, Chunquan Zheng, Le Shi
Background: Chronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while its role in pathogenesis of CRS has yet to be revealed. This research study was designed to investigate the relationship between the expression level and biologic role of LRRK2 in CRS. Methods: Expression of LRRK2 mRNA and noncoding repressor of NFAT (NRON) were examined by qRT-PCR...
2018: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29543677/fluorescent-in-situ-hybridization-for-tp53-in-the-diagnosis-of-pediatric-osteogenic-sarcoma
#15
Paula Marrano, Mary Shago, Gino R Somers, Paul S Thorner
Osteogenic sarcoma (OS) is the most common malignant bone tumor in children and adolescents. Despite advances in molecular genetic characterization of pediatric and adult tumors, the diagnosis of OS still depends almost entirely on light microscopy. The lack of consistent genetic changes in OS has greatly hindered the development of any diagnostic molecular test. Recently, whole-genome sequencing has shown that ~50% of cases of OS have a translocation involving the TP53 gene with breakpoints confined to the first intron...
March 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29540600/baculovirus-ac102-is-a-nucleocapsid-protein-that-is-crucial-for-nuclear-actin-polymerization-and-nucleocapsid-morphogenesis
#16
Susan E Hepp, Gina M Borgo, Simina Ticau, Taro Ohkawa, Matthew D Welch
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the type species of alphabaculoviruses, is an enveloped DNA virus that infects lepidopteran insects and is commonly known as a vector for protein expression and cell transduction. AcMNPV belongs to a diverse group of viral and bacterial pathogens that target the host cell actin cytoskeleton during infection. AcMNPV is unusual, however, in that it absolutely requires actin translocation into the nucleus early in infection, and actin polymerization within the nucleus late in infection coincident with viral replication...
March 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29500147/a-retrospective-study-of-double-hit-lymphomas-in-elderly-patients-aged-70-years-overall-outcomes
#17
Christie Hancock, Phillip Knouse, Imad Almanaseer, Jacob Bitran
BACKGROUND: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29484117/paeoniflorin-regulates-osteoclastogenesis-and-osteoblastogenesis-via-manipulating-nf-%C3%AE%C2%BAb-signaling-pathway-both-in-vitro-and-in-vivo
#18
Yanmao Wang, Jiezhi Dai, Yu Zhu, Wanrun Zhong, Shengdi Lu, Hua Chen, Yimin Chai
The metabolic balance between synthesis and resorption of the bone is maintained by osteoblasts and osteoclasts, respectively. Identification of agents that stimulate bone formation and suppress excessive osteoclast formation, may aid in preventing and treating conditions like osteoporosis and periprosthetic loosening. Paeoniflorin is a natural product derived from Paeonia lactiflora Pall with anti-inflammatory, analgesic, and diuretic properties. However, the effect of paeoniflorin on osteoclastogenesis and osteoblastogenesis is unknown...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29481959/inhibition-of-nuclear-translocation-of-notch-intracellular-domain-nicd-by-diosgenin-prevented-atherosclerotic-disease-progression
#19
Ambika Binesh, Sivasithambaram Niranjali Devaraj, Halagowder Devaraj
Notch signaling plays a pivotal role in homeostasis and cardiovascular development. The role of notch signaling in atherosclerosis cannot be complete without analysing the key role of notch in macrophages, which trigger the inflammatory response and subsequent plaque formation in atherosclerosis. Diosgenin showed its anti-atherosclerotic property by the unifying mechanism of suppressing the expression of notch signaling pathway, particularly the nuclear translocation of notch intracellular domain (NICD) in aorta and in differentiated macrophage cells...
May 2018: Biochimie
https://www.readbyqxmd.com/read/29472448/double-stranded-dna-break-polarity-skews-repair-pathway-choice-during-intrachromosomal-and-interchromosomal-recombination
#20
Alexanda K Ling, Clare C So, Michael X Le, Audrey Y Chen, Lisa Hung, Alberto Martin
Activation-induced cytidine deaminase (AID) inflicts DNA damage at Ig genes to initiate class switch recombination (CSR) and chromosomal translocations. However, the DNA lesions formed during these processes retain an element of randomness, and thus knowledge of the relationship between specific DNA lesions and AID-mediated processes remains incomplete. To identify necessary and sufficient DNA lesions in CSR, the Cas9 endonuclease and nickase variants were used to program DNA lesions at a greater degree of predictability than is achievable with conventional induction of CSR...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
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